Systemic or Vaginal Hormone Therapy After Early Breast Cancer: A Danish Observational Cohort Study

Søren Cold et al (J Natl Cancer Inst. 2022 Jul 20;djac112. doi: 10.1093/jnci/djac112. ) studied longitudinally a national cohort of postmenopausal women, diagnosed 1997-2004 with early-stage invasive estrogen receptor-positive nonmetastatic breast cancer (BC), who received no treatment or 5 years of adjuvant endocrine therapy. Some women suffering from  genitourinary syndrome were treated with vaginal estrogen therapy (VET) or menopausal hormone therapy (MHT). The authors ascertained prescription data on VET or MHT, from a national prescription registry and evaluated mortality and risk of recurrence.

Results: Among 8461 women who had not received VET or MHT before BC diagnosis, 1957 and 133 used VET and MHT, respectively, after diagnosis. Median follow-up was 9.8 years for recurrence and 15.2 years for mortality.

The adjusted relative risk of recurrence was 1.08 (95% confidence interval [CI] = 0.89 to 1.32) for VET (1.39 [95% CI = 1.04 to 1.85 in the subgroup receiving adjuvant aromatase inhibitors]) and 1.05 (95% CI = 0.62 to 1.78) for MHT. The adjusted hazard ratios for overall mortality were 0.78 (95% CI = 0.71 to 0.87) and 0.94 (95% CI = 0.70 to 1.26) for VET and MHT, respectively.

Conclusions: In postmenopausal women treated for early-stage estrogen receptor-positive BC, neither VET nor MHT was associated with increased risk of recurrence or mortality. A subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving VET with adjuvant aromatase inhibitors.